Adenylyl cyclases (ACs) convert ATP into the classical second messenger cyclic adenosine monophosphate (cAMP). Cardiac ACs, specifically AC5, AC6, and AC9, regulate cAMP signaling controlling functional outcomes such as heart rate, contractility and relaxation, gene regulation, stress responses, and glucose and lipid metabolism. With so many distinct functional outcomes for a single second messenger, the cell creates local domains of cAMP signaling to correctly relay signals. Targeting of ACs to A-kinase anchoring proteins (AKAPs) not only localizes ACs, but also places them within signaling nanodomains, where cAMP levels and effects can be highly regulated. Here we will discuss the recent work on the structure, regulation and physiological functions of AC9 in the heart, where it accounts for <3% of total AC activity. Despite the small contribution of AC9 to total cardiac cAMP production, AC9 binds and regulates local PKA phosphorylation of Yotiao-IKs and Hsp20, demonstrating a role for nanometric targeting of AC9.
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Cover Image
Cover Image
The second messenger 3′,5′-cyclic nucleoside adenosine monophosphate (cAMP) plays a key role in signal transduction across prokaryotes and eukaryotes. In this issue Klausen and colleagues (1733–1748) provide an overview about the optogenetic tools and biosensors used to explore the subcellular organization of cAMP signalling. The cover image depicts time projection (colour represents time) of a head-tethered transgenic mouse sperm expressing the photo-activated adenylate cyclase bPAC. Image courtesy of Dagmar Wachten.
Nanometric targeting of type 9 adenylyl cyclase in heart
Autumn N. Marsden, Carmen W. Dessauer; Nanometric targeting of type 9 adenylyl cyclase in heart. Biochem Soc Trans 20 December 2019; 47 (6): 1749–1756. doi: https://doi.org/10.1042/BST20190227
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